Reaction with acetonides

Nonanedione, another 1,3-difunctional target molecule, may be obtained from the reaction of hexanoyl chloride with acetonide anion (disconnection 1). The 2,4-dioxo substitution pattern, however, is already present in inexpensive, symmetrical acetylacetone (2,4-pentanedione). Disconnection 2 would therefore offer a tempting alternative. A problem arises because of the acidity of protons at C-3 of acetylacetone. This, however, would probably not be a serious obstacle if one produces the dianion with strong base, since the strongly basic terminal carbanion would be a much more reactive nucleophile than the central one (K.G. Hampton, 1973 see p. 9f.). 

Steroidal cis vicinal diols at the 1,2-, ° 2,3-, ° 5,6- or 11,12- " positions can be selectively protected as acetonides, prepared by reaction with acetone at room temperature or at higher temperatures in the presence of hydrochloric, perchloric or -toluenesulfonic acids. Cis nonvicinal-diols can be similarly protected. 

Diols yield acetonides, even in the presence of a 17oc-hydroxylgroup. Reaction with acetone in the presence of zinc chloride as catalyst leads to the formation of diacetone alcohol acetal as a by-product. ... 

However, 17a,21-acetonides (103), as well as acetals of other ketones or aldehydes, can be easily prepared by acid-catalyzed exchange reaction with dimethoxypropane or other alkyl acetals in dimethylformamide or benzene. Enol etherification of the A -S-ketone also occurs with the former procedure. 

Intermediate 8, the projected electrophile in a coupling reaction with intermediate 7, could conceivably be derived from iodolactone 16. In the synthetic direction, cleavage of the acetonide protecting group in 16 with concomitant intramolecular etherification could result in the formation of the functionalized tetrahydrofuran ring of... 

Protective Groups for Diols. Diols represent a special case in terms of applicable protecting groups. 1,2- and 1,3-diols easily form cyclic acetals with aldehydes and ketones, unless cyclization is precluded by molecular geometry. The isopropylidene derivatives (also called acetonides) formed by reaction with acetone are a common example. 

It is of interest that there exists a considerable amount of flexibility as to the substituent at C-21 in the acetonide series. For example, formation of the acetonide from 241 affords intermediate 242. Reaction with methanesulfonyl chloride gives the corresponding mesylate (243). Displacement... 

The reaction appears to be general and the additions are regiospecific and stereoselective. The product from the reaction with 2-propanol has been used for the synthesis of cis-chrysanthemic acid,8 and the product with methanol has been used for the construction of novel 2, 3 -dideoxy-3 -hydroxymethylnucleosides.9 In addition, ethane-1,2-diol provides the expected photoadduct as a 1 1 mixture of the two possible diastereoisomers, and these can be easily separated as their acetonides, to provide compounds with three contiguous chiral centers emanating from furan-ones with only one chiral center.9 More recently, we have shown that photoinduced-... 

In order to test these assumptions Heathcock prepared different chiral ketones. Thus, the aldol condensation of the fructose-derived ketone and the acetonide of (/ )-glyceraldehyde gave poor results in the double stereodifferentiation, since an almost equal mixture of the two jyn-aldols 68a and 68b were obtained. However, the reaction with the (5)-aldehyde gave only one syn adduct (69a) (Scheme 9.22) ... 

The increased enantioselectivity of 88 is also apparent in reactions with chiral aldehydes (Figure 28). p-Alkoxypropionaldehydes 90 were relatively poor substrates when 36 was used.3 The best selectivity ever obtained for syn diastereomer 91 in the matched double asymmetric reactions was 89 11 [(S,S)-36 and 90a], whereas the best selectivity for anti diastereomer 92 was 87 13 [reaction of 90b and (R,R)-36. In contrast, the allylborations of 90a,b with the new reagent 88 now proceed with up to 97 3 selectivity for either product diastereomer. Even more impressive results were obtained with glyceraldehyde acetonide (23) the matched double asymmetric reaction leading to 29 now proceeds with 300 1 diastereoselectivity, while the mismatched combination leading to 30 proceeds with 50 1 selectivity. 

Buchanan et al. (48) reported a new route to the synthesis of the chiral hydroxy-pyrrolidines 234 and 238 from D-erythrose (230) via an intramolecular cycloaddition of an azide with an alkene (Scheme 9.48). Wittig reaction of the acetonide 230 with (carbethoxyethylene)triphenylphosphorane gave the ( ) and (Z) alkenes 231 and 232. On conversion into the triflate followed by its reaction with KN3, the ( ) isomer 231 allowed the isolation of the triazoline 234 in 68% overall yield, which on treatment with sodium ethoxide afforded the diazo ester 235 in 86% yield. 

Macrocyclic lactonization. co-Hydroxy acids are converted into the corresponding lactones by reaction with cyanuric chloride and triethylaminc in acetone or acetonitrile at 25°.1 Isolated yields of 13-, 16-, 17-, and 19-membered lactones are 70, 68, 85, and 33%, respectively. An example is the lactonization of aleuritic acid (I) to the lactone acetonide 2. 

To address limitations in the use of glyceraldehyde acetonide (43) as a three-carbon chiral building block, butane-2,3-diacetal-protected glyceraldehyde (44, R1 = R2 = H) has been prepared. It undergoes diastereoselective aldol reactions with a range of carbonyl compounds esters, thioesters, and ketones. The work has been extended (g) to other derivatives such as the a-substituted aldehyde (44, R1 = Me, allyl) and the methyl ketone (44, R2 = Me).122a,b... 

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